Heavyweight titleholder Deontay Wilder's defense against mandatory challenger Alexander Povetkin was called off Sunday in the wake of Povetkin's positive test for the banned substance meldonium.

Wilder and Povetkin were scheduled for their much-anticipated fight on May 21 at the Khodynka Ice Palace in Moscow, but in a Voluntary Anti-Doping Association urine test conducted April 27 in Chekhov, Russia, Povetkin tested positive for meldonium. The test results came to light Friday when the VADA sent letters to both camps and the WBC, whose title Wilder holds, disclosing them.

Wilder and his team have been in Sheffield, England, for the past two weeks training and adjusting to several hours of time difference. They were scheduled to fly to Moscow on Sunday afternoon but did not board their flight and were making plans to return to the United States despite having not heard from the WBC on the matter, a member of Wilder's team told ESPN.com.

Hours after Wilder and his team skipped their flight, the WBC, having little choice with the titleholder preparing to return home, announced the fight was off and called it a postponement.

"The World Boxing Council is diligently addressing the positive test result from the [WBC's] clean boxing program for mandatory challenger Alexander Povetkin," WBC president Mauricio Sulaiman said in a statement. "Keeping the priority of safety and also the principle of justice, the WBC will continue the investigation into the case. Consequently, the event scheduled for May 21 in Moscow is hereby officially postponed. The WBC will be releasing more information in the coming days regarding the final ruling on the matter."

Wilder, who embraced going to foreign territory to defend his title, was upset that the fight was called off.

"I'm very disappointed that due to Povetkin's failed drug test the fight is not going to happen on May 21 in Moscow," Wilder said in a statement. "I had worked very hard to prepare myself for this important title defense, spending the last two weeks training in England to get accustomed to fighting in Europe. I wanted to give the fans a great show, but we understand the WBC's position that the fight occur on an even playing field.

"This is a huge disappointment and a setback to my goals in boxing. I want to be an active heavyweight champion and it is still my goal to collect all the belts and become the undisputed heavyweight champion of the world."

Meldonium is the same drug for which tennis star Maria Sharapova and many other athletes recently tested positive. It was approved to be added to the banned substance list by the World Anti-Doping Agency in September, and the ban went into effect Jan. 1. Meldonium is used to increase blood flow and carry more oxygen to muscles, thereby enhancing stamina, a trait boxers would want in a long fight.

"The guy tested positive for a dangerous drug and the health and safety of Deontay was paramount, so the fight could not take place on May 21," Wilder promoter Lou DiBella told ESPN.com. "Deontay would have fought King Kong without any regard for what substance was being used, but Povetkin's use of this banned substance and the breach of the contract deprived Deontay of an opportunity to defend his title on a fair playing field. As a result, Deontay has suffered significant damages.

"He has gone through his entire training camp and expended a tremendous amount of time and money and energy. It's awful."

Povetkin said he is clean and took meldonium before the ban went into effect.

"I haven't taken anything or consumed anything, so I've got nothing to fear," he said.

Alexander Povetkin's chance at Deontay Wilder's title has been postponed following the Russian heavyweight's positive test for meldonium. Dmitry Korotayev/Epsilon/Getty Images

Andrey Ryabinsky of World of Boxing, Povetkin's promoter, said the fight would be rescheduled while the rest of the card will go forward. A cruiserweight world title unification bout between Russia's Denis Lebedev (28-2, 21 KOs) and Victor Emilio Ramirez (22-2-1, 17 KOs), of Argentina, has been moved from the co-feature to the main event.

"Any talk from Ryabinsky of a rescheduled date is both unfounded and premature," DiBella said. "We need to sit back and await further rulings from the WBC, but we will weigh all of our options."

There is a lot of money at stake. Based on Ryabinsky's winning purse bid of $7.15 million, Wilder was due $4,504,500 to Povetkin's $1,930,500 with the remaining 10 percent -- $715,000 -- going to the winner. With no fight, the purses won't be paid and a lawsuit is likely to ensue; Wilder's purse is sitting in escrow in a United States bank, according to his camp.

If there is a lawsuit, Ryabinsky could have issues mirroring a 2014 situation he was in.

Lebedev, who is promoted by Ryabinsky, was due to face Guillermo Jones in a rematch in Russia, but with the fighters in their dressing rooms hours before the fight, Jones tested positive for a banned diuretic, which is typically used as a masking agent for steroids. The fight was canceled, and Ryabinsky later won a judgment against Jones promoter Don King for the money he and Lebedev were owed for the bout.

Ryabinsky said Povetkin's levels of meldonium were very low and that the traces in his system were left over from when he took it in September.

"He has not taken it since Jan. 1. The situation is ambiguous," Ryabinsky told Russia's TASS news agency before the fight was called off. "The blood sample was taken in April this year."

However, Povetkin was tested by the VADA on April 7, 8 and 11, and each of those tests came back negative for any banned substances, according to two letters ESPN.com obtained in which the VADA disclosed those test results to both sides and the WBC. Those results indicate that meldonium apparently entered Povetkin's system after the ban was in place.

Wilder (36-0, 35 KOs), 30, a 2008 U.S. Olympic bronze medalist from Tuscaloosa, Alabama, was supposed to make his fourth title defense against Russia's Povetkin (30-1, 22 KOs), 36, a 2004 Olympic gold medalist. Povetkin loomed as Wilder's most significant opponent, and the fight is one of the significant bouts that could be made in the heavyweight division.